Download Clinical Manifestations

Disseminated Intravascular
Coagulation
Thrombotic microangiopathy refers to a
heterogeneous group of conditions, including
disseminated intravascular coagulation (DIC), that
result in consumption of clotting factors, platelets,
and anticoagulant proteins. Consequences of this
process
include
widespread
intravascular
deposition of fibrin, leading to tissue ischemia and
necrosis, a generalized hemorrhagic state, and
hemolytic anemia.
Clinical Manifestations
DIC accompanies a severe systemic disease process,
usually with shock. Bleeding frequently first occurs from
sites of venipuncture or surgical incision. The skin may
show petechiae and ecchymoses. Tissue necrosis may
involve many organs and can be seen as infarction of
large areas of skin, subcutaneous tissue, or kidneys.
Anemia caused by hemolysis may develop rapidly, owing
to microangiopathic hemolytic anemia.
Laboratory Findings
There is no well-defined sequence of events. Certain
coagulation factors (factors II, V, and VIII, and fibrinogen)
and platelets may be consumed by the ongoing
intravascular clotting process, with resultant prolongation
of the prothrombin, partial thromboplastin, and thrombin
times. Platelet counts may be profoundly depressed. The
blood smear may contain fragmented and burr- and
helmet-shaped red blood cells (schistocytes). In addition,
because the fibrinolytic mechanism is activated, fibrinogen
degradation products (FDPs, D-dimers) appear in the
blood. The D-dimer is formed by fibrinolysis of a crosslinked fibrin clot. The D-dimer assay is as sensitive as the
FDP test and more specific for activation of coagulation
and fibrinolysis
Treatment
The 1st 2 steps in the treatment of DIC are the most
critical: (1) treat the trigger that caused DIC and (2) restore
normal homeostasis by correcting the shock, acidosis, and
hypoxia that usually complicate DIC. If the underlying
problem can be controlled and the patient stabilized,
bleeding quickly ceases, and there is improvement of the
abnormal laboratory findings. Blood components are used
for replacement therapy in patients with hemorrhage and
may consist of platelet infusions (for thrombocytopenia),
cryoprecipitate (for hypofibrinogenemia), and/or fresh
frozen plasma (for replacement of other coagulation
factors and natural inhibitors).
In DIC associated with sepsis, a controlled trial of drotrecogin
alpha (activated protein C concentrate [APC]) in adults with sepsis
showed a statistically significant survival advantage in those
treated with APC. Clinical trials using protein C concentrate in
purpura fulminans and APC in children with sepsis syndrome have
not shown a statistically significant improvement.
The role of heparin in DIC is limited to patients who have vascular
thrombosis in association with DIC or who require prophylaxis
because they are at high risk for venous thromboembolism.
The prognosis of patients with DIC is primarily dependent on the
outcome of the treatment of the primary disease and prevention
of end-organ damage
Idiopathic (Autoimmune) Thrombocytopenic
Purpura
The most common cause of acute onset of
thrombocytopenia in an otherwise well child is
(autoimmune) idiopathic thrombocytopenic purpura
(ITP).
Pathogenesis
Why some children develop the acute presentation of an
autoimmune disease is unknown. The exact antigenic target
for most such antibodies in most cases of childhood acute ITP
remains undetermined. although in chronic ITP most patients
demonstrate antibodies against the platelet glycoprotein
complexes. After binding of the antibody to the platelet
surface, circulating antibody-coated platelets are recognized
by the receptor on splenic macrophages, ingested, and
destroyed. Most common viruses have been described in
association with ITP, including Epstein-Barr virus and HIV.
Epstein-Barr virus-related ITP is usually of short duration and
follows the course of infectious mononucleosis.
Clinical Manifestations
The classic presentation of ITP is a previously healthy 1-4 yr
old child who has sudden onset of generalized petechiae and
purpura. The parents often state that the child was fine
yesterday and now is covered with bruises and purple dots.
Often there is bleeding from the gums and mucous
membranes, particularly with profound thrombocytopenia
There is a history of a preceding viral infection 1-4 wk before
the onset of thrombocytopenia. Findings on physical
examination are normal, other than the finding of petechiae
and purpura. Splenomegaly, lymphadenopathy, bone pain,
and pallor are rare.
Outcome
Severe bleeding is rare (<3% of cases in 1 large international
study). In 70-80% of children who present with acute ITP,
spontaneous resolution occurs within 6 mo. Therapy does
not appear to affect the natural history of the illness. Fewer
than 1% of patients develop an intracranial hemorrhage.
There is no evidence that therapy prevents serious
bleeding. Approximately 20% of children who present
with acute ITP go on to have chronic ITP. The
outcome/prognosis may be related more to age, as ITP in
younger children is more likely to resolve whereas the
development of chronic ITP in adolescents approaches
50%.
Laboratory Findings
Severe thrombocytopenia is common, and platelet size is
normal or increased, reflective of increased platelet turnover.
In acute ITP, the hemoglobin value, white blood cell (WBC)
count, and differential count should be normal. Hemoglobin
may be decreased if there have been profuse nose bleeds or
menorrhagia. Bone marrow examination shows normal
granulocytic and erythrocytic series, with characteristically
normal or increased numbers of megakaryocytes. Some of
the megakaryocytes may appear to be immature and are
reflective of increased platelet turnover.
Indications for bone marrow aspiration/biopsy include an
abnormal WBC count or differential or unexplained
anemia as well as findings on history and physical
examination suggestive of a bone marrow failure
syndrome or malignancy. Other laboratory tests should be
performed as indicated by the history and physical
examination. In adolescents with new-onset ITP, an
antinuclear antibody test should be done to evaluate for
SLE.
Treatment
There are no data showing that treatment affects either
short- or long-term clinical outcome of ITP. Many patients
with new-onset ITP have mild symptoms, with findings limited
to petechiae and purpura on the skin, despite severe
thrombocytopenia. Compared with untreated control
subjects, treatment appears to be capable of inducing a more
rapid rise in platelet count to the theoretically safe level,
although there are no data indicating that early therapy
prevents intracranial hemorrhage. Antiplatelet antibodies
bind to transfused platelets as well as they do to autologous
platelets. Thus, platelet transfusion in ITP is usually
contraindicated unless life-threatening bleeding is present.
Initial approaches to the management of ITP include the
following:
1 No therapy other than education and counseling of the
family and patient for patients with minimal, mild, and
moderate symptoms, as defined earlier.
2 Intravenous immunoglobulin (IVIG). IVIG at a dose of
0.8-1.0 g/kg/day for 1-2 days induces a rapid rise in
platelet count (usually >20 x 109/L) in 95% of patients
within 48 hr.
3.Prednisone. Corticosteroid therapy has been used for
many years to treat acute and chronic ITP in adults and
children. Doses of prednisone of 1-4 mg/kg/24 hr appear
to induce a more rapid rise in platelet count than in
untreated patients with ITP.
4.Intravenous anti-D therapy. For Rh positive patients, IV
anti-D at a dose of 50-75 ?g/kg causes a rise in platelet
count to >20 x 109/L in 80-90% of patients within 48-72 hr.
In the special case of intracranial hemorrhage,
multiple modalities should be used, including platelet
transfusion, IVIG, high-dose corticosteroids, and
prompt consultation by neurosurgery and surgery.
The role of splenectomy in ITP should be reserved for 1 of
2 circumstances. The older child (≥4 yr) with severe ITP
that has lasted >1 yr (chronic ITP) and whose symptoms
are not easily controlled with therapy is a candidate for
splenectomy. Splenectomy must also be considered when
life-threatening hemorrhage (intracranial hemorrhage)
complicates acute ITP, if the platelet count cannot be
corrected rapidly with transfusion of platelets and
administration of IVIG and corticosteroids.
Chronic Idiopathic Thrombocytopenic Purpura
Approximately 20% of patients who present with acute ITP
have persistent thrombocytopenia for >12 mo and are said
to have chronic ITP. At that time, a careful re-evaluation for
associated disorders should be performed, especially for
autoimmune disease, such as SLE; chronic infectious
disorders, such as HIV; and non immune causes of chronic
thrombocytopenia, such as type 2B and platelet-type von
Willebrand
disease,
X-linked
thrombocytopenia,
autoimmune lymphoproliferative syndrome, common
variable immunodeficiency syndrome.